cis-4-Carboxy-6-(mercaptomethyl)-3, 4, 5, 6-tetrahydropyrimidin-2 (1H)-one, a potent inhibitor of mammalian dihydroorotase

…, SM Mong, RK Johnson, BW Metcalf

Index: Adams, Jerry L.; Meek, Thomas D.; Mong, Shau-Ming; Johnson, Randall K.; Metcalf, Brian W. Journal of Medicinal Chemistry, 1988 , vol. 31, # 7 p. 1355 - 1359

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Citation Number: 31

Abstract

A series of cis-and trans-4-carboxy-3, 4, 5, 6-tetrahydropyrimidin-2 (lH)-ones possessing either a carboxy, hydroxymethyl, or mercaptomethyl substituent at C-6 were prepared and tested for their ability to inhibit mammalian dihydroorotase. Of these compounds, only the cis- 6-mercaptomethyl compound, cis-1, was found to be a potent competitive inhibitor of the enzyme (Ki= 140 nM at pH 7.4 and 8.5) when assayed in the direction of dihydro-L-orotate ...